A multitude of self-monitoring and laboratory tests for analytes of interest are performed on biological samples for diagnosis, screening, disease staging, forensic analysis, pregnancy testing, and drug testing, among others. While a few qualitative tests, such as glucose, prothrombin and pregnancy tests, have been reduced to simple kits for a patient's home use, the majority of quantitative tests still require the expertise of trained technicians in a laboratory setting using sophisticated instruments. Laboratory testing increases the cost of analysis and delays the patient's or clinician's receipt of the results. In many circumstances, this delay can be detrimental to the patient's condition or prognosis, such as for example the analysis of markers indicating myocardial infarction and heart failure. In these and similar critical situations, it is advantageous to perform such analyses at the point-of-care, accurately, inexpensively and with minimal delay.
Self-monitoring tests are generally performed using in-home sample analysis systems, e.g., blood glucose monitoring devices. In-home analysis systems generally include a reusable reading apparatus that performs sample tests using a plurality of disposable devices (e.g., electrochemical test sensors or test strips) that can be loaded into the reading apparatus. An example of such a system is the PRECISION™ line of blood glucose and ketone body monitoring systems sold by Abbott Diabetes Care, Inc., Alameda, Calif., USA. Each individual electrochemical test sensor typically includes a substrate that is formed as a thin, rectangular strip of non-conductive material, and a plurality of carbon-layer electrodes deposited on the substrate with one electrode functioning as the reference electrode and one electrode functioning as the working electrode for the test sensor. In a reaction area of the substrate, an enzyme is deposited on the working electrode, and when the patient sample is exposed to the enzyme, the analyte, e.g., glucose, undergoes a chemical reaction, which produces a measurable electrical response.
Point-of-care sample analysis systems are generally based on a reusable reading apparatus that performs sample tests using a disposable device (e.g., a cartridge or strip) that contains analytical elements (e.g., electrodes or optics for sensing analytes such as, for example, pH, oxygen, glucose, or ketone body). The disposable device can optionally include fluidic elements (e.g., conduits for receiving and delivering the sample to the electrodes or optics), calibrant elements (e.g., fluids for standardizing the electrodes with a known concentration of the analyte), and dyes with known extinction coefficients for standardizing optics. In operation, the user may select a disposable device with the required panel of tests (e.g., electrolytes, metabolites, cardiac markers and the like), draw a sample, dispense it into the device, optionally seal the device, and insert the device into the reading apparatus to communicate the data to an LIS/HIS for analysis. An example of such a system is the i-STAT® system sold by Abbott Point-of-Care, Inc., Princeton, N.J., USA. The i-STAT® portable blood analysis system typically comprises Wi-Fi-enabled reader instruments that work in conjunction with single-use blood testing cartridges that contain sensors for various analytes. For further information on the i-STAT® portable blood analysis system, see http://www.abbottpointofcare.com/.
Self-monitoring and point-of-care sample testing systems eliminate the time-consuming need to send a sample to a central laboratory for testing. For instance, self-monitoring generally requires frequent measurements of a concentration of a particular analyte in a body fluid e.g., blood, of a patient, and the in-home analysis systems allow the patient to obtain a reliable qualitative results frequently throughout the day. Additionally, point-of-care sample testing systems allow a user e.g. a nurse and physician, at the bedside of a patient, to obtain reliable, quantitative, analytical results, comparable in quality to that which would be obtained in a laboratory.
Analyzers for self-monitoring and point-of-care testing, such as a self-contained disposable sensing device or cartridge and a reader or instrument, are further described in U.S. Pat. No. 7,418,285 to Ghesquiere et al. and U.S. Pat. No. 5,096,669 to Lauks, et al., the entireties of which are incorporated herein by reference. In general operation of the analyzers, a fluid sample to be measured is drawn into a device and the device is inserted into the reader through a slotted opening. Data generated from measurements performed by the reader may be output to a display and/or other output device, such as a printer, or, as described in greater detail below, via a wireless network connection. The disposable device may contain sensing arrays and several cavities and conduits that perform sample collection, provide reagents for use in measurement and sensor calibration, and transport fluids to and from the sensors. Optionally, reagents may be mixed into the sample for testing. Sensing arrays in the device measure the specific chemical species in the fluid sample being tested. The electrochemical sensors are exposed to and react with the fluid sample to be measured generating electrical currents and potentials indicative of the measurements being performed. The electrochemical sensors may be constructed dry and when the calibrant fluid flows over the electrochemical sensors, the sensors easily “wet up” and are operational and stable for calibration and composition measurements. These characteristics provide many packaging and storage advantages, including a long shelf life. Each of the sensing arrays may comprise an array of conventional electrical contacts, an array of electrochemical sensors, and circuitry for connecting individual sensors to individual contacts. The electrical signals are communicated to a reader enabled to perform calculations and to display data, such as the concentration of the results of the measurement.
Although the particular order in which the sampling and analytical steps occur may vary between different self-monitoring systems, point-of-care systems, and providers, the objective of providing rapid sample test results in close proximity to a patient remains. The reading apparatus (e.g., Precision Xtra® Blood Glucose Monitoring System, i-STAT® analyzer or other analyzer) may then perform a test cycle (i.e., all the other analytical steps required to perform the tests). Such simplicity gives the patient or physician quicker insight into the patient's physiological status and, by reducing the time for monitoring or diagnosis, enables a quicker decision by the patient or physician on disease management or appropriate treatment, thus enhancing the likelihood of a successful patient treatment.
In the emergency room and other acute-care locations within a hospital, the types of sample tests required for individual patients can vary widely. Thus, point-of-care systems generally offer a range of disposable devices configured to perform different sample tests, or combinations of such tests. For example, for blood analysis devices, in addition to traditional blood tests, including oxygen, carbon dioxide, pH, potassium, sodium, magnesium, calcium, chloride, phosphate, hematocrit, glucose, urea (e.g., BUN), creatinine and liver enzymes, other tests may include, for example, prothrombin time (PT), activated clotting time (ACT), activated partial thromboplastin time (APTT), troponin, creatine kinase MB (CKMB), and lactate. Although devices typically contain between one and ten tests, it will be appreciated by persons of ordinary skill in the art that any number of tests may be contained in a device.
A given hospital may use numerous different types of test devices and test instruments at multiple point-of-care testing locations within the hospital. These locations can include, for example, an emergency room (ER), a critical care unit (CCU), a pediatric intensive care unit (PICU), an intensive care unit (ICU), a renal dialysis unit (RDU), an operating room (OR), a cardiovascular operating room (CVOR), general wards (GW), and the like. Other non-hospital-based locations where medical care is delivered, include, for example, MASH units, nursing homes, and cruise, commercial, and military ships.
In some cases, test strips and cartridges have a shelf life, which may vary widely depending on the specific test strip or cartridge as well as upon storage conditions. For example, some cartridges may have a shelf life of about six to about nine months when refrigerated, but a much more limited shelf life, e.g., about two weeks at room temperature, or, more specifically, about ten weeks at up to about 30° C. As a result, hospitals typically store cartridges at a central refrigerated location, and deliver cartridges to specific locations as demand requires. These locations can include, for example, an emergency room (ER), critical care unit (CCU), pediatric intensive care unit (PICU), intensive care unit (ICU), renal dialysis unit (RDU), operating room (OR), cardiovascular operating room (CVOR) and general wards (GW). These locations may or may not have available refrigerated storage, and this will impact product lifetime and, as a result, the inventory they will hold. Further complicating device management is the fact that a given user, such as the patient, may store the test strips in an improper manner, e.g., at an unsuitable temperature or humidity, or a user, such as a hospital, may use multiple types of cartridges, each having a different shelf life. Alternatively, the user may be a physician's office laboratory or visiting nurse service. However, the need to ensure quality remains the same.
U.S. Patent Appl. No. US 2009/0119047 to Zelin et al., the entirety of which is incorporated herein by reference, discloses an improved quality assurance system and method for point-of-care testing. It provides quality assurance for laboratory quality tests performed by a blood analysis system at the point of patient care without the need for running liquid-based quality control materials on the analysis system. Quality assurance of a quantitative physiological sample test system is performed without using a quality control sample by monitoring the thermal and temporal stress of a component used with the test system. Alert information is generated that indicates that the component has failed quality assurance when the thermal and temporal stress exceeds a predetermined thermal-temporal stress threshold.
U.S. Pat. No. 7,612,325 to Watkins Jr., et al., the entirety of which is incorporated herein by reference, discloses electrical sensor for monitoring degradation of products from environmental stressors and describes an environmental degradation sensor for environmentally sensitive products such as food, pharmaceuticals or cosmetic products provides the degraded state and estimated remaining life of the product. The sensor is made of a polymeric matrix and conductive filler. A control agent, selected to adjust a reaction rate of the sensor to environmental conditions, allows correlation of an electrical property of the sensor to a degraded state of the product.
Application Note 2004-2, “A Comparison of Relative Humidity Sensing Technologies,” Hygrometrix Inc., 2004, the entirety of which is incorporated herein by reference, discloses that the transduction of water vapor concentration into an electrical measurement by a sensing film comprises three processes: (i) physical and chemical interaction of water vapor molecules with the film surface; (ii) surface and bulk modifications of the film due to water vapor accumulation on and diffusion into the film; and (iii) electrical measurement of a key electrical or mechanical property of the film that changes due to its interaction with water vapor. The sensing films are typically made of polyelectrolyte, polymers, and porous ceramic.
In general, the principles of operation for existing types of time/temperature and time/humidity indicators can be categorized as physical, chemical and electrical. Examples of physical and chemical methods include color change of polymeric materials, chemical reactions of two elements, physical masking of a marker, melting of a temperature sensitive material and the like.
However, the use of many existing indicators adds significant cost and complexity to the devices they are intended to monitor. This is a particularly apparent issue for single-use blood testing cartridges and electrochemical strip devices, e.g., glucose blood testing strips used by diabetics. Consequently, the need remains for improved low cost time-temperature or time-humidity indicators that are amenable to direct integration into a device manufacturing work flow.